Research study · The Journal of Arthroplasty · 2026
A Synthetic Form of Cannabinoid Does Not Decrease Opioid Use After Total Knee Arthroplasty: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Study
A 2026 randomized controlled trial in The Journal of Arthroplasty tested opioid in postoperative pain. No differences in in-hospital MME consumed between sTHC (40.1 +/- 74.8) and placebo (38.8 +/- 76.4, P = 0.901). This study suggests that a low dose of synthetic THC does not reduce opioid use or improve pain and sleep outcomes.
Study overview
In this prospective, triple-blind, placebo-controlled trial, oral dronabinol (2.5 mg twice daily) failed to reduce opioid consumption or improve secondary pain and sleep outcomes following primary total knee arthroplasty. These findings suggest that standard low-dose synthetic THC offers no significant adjunctive benefit for acute postoperative pain management in cannabis-naïve surgical patients.
Findings
No differences in in-hospital MME consumed between sTHC (40.1 +/- 74.8) and placebo (38.8 +/- 76.4, P = 0.901). No differences in total MME noted at two weeks between sTHC (383.6 +/- 309.8) and placebo (367.6 +/- 246.3, P = 0.717). No significant differences in self-reported pain, sleep, nausea/vomiting, range of motion, or PROMs at assessed time points. Study was discontinued early based on an interim analysis of futility.
Why this matters
This study suggests that a low dose of synthetic THC does not reduce opioid use or improve pain and sleep outcomes after knee surgery. It leaves open questions about other doses, forms, or populations where different results might be found.
Abstract
Background: Self-reported cannabis use in patients undergoing total knee arthroplasty (TKA) has increased since its legalization. Despite endorsement, its efficacy has never been studied in a prospective randomized study in orthopaedic surgery. The purpose of this study was to determine whether a synthetic delta-9-tetrahydrocannabinol (sTHC), dronabinol, decreases opioid use after TKA. Methods: There were 163 patients who underwent primary unilateral TKA who were prospectively randomized into receiving dronabinol (2.5 mg twice a day, n = 81) versus a placebo pill (2.5 mg twice a day, n = 82) as an adjunct to pain management. Patients, providers, our statistician, and the research team were blinded to the groups. Patients were cannabis naïve and had drug screening prior to surgery. Patients received our standard perioperative multimodal pain regimen (including opioids) regardless of randomization. The primary outcome was opioid morphine milligram equivalents (MME) at two weeks. Secondary outcomes included self-reported pain, sleep scores, nausea/vomiting, knee range of motion, and patient-reported outcomes. Patients were followed for six weeks after TKA. Statistical significance was accepted at P <= 0.05. Results: There were no differences for in-hospital MME consumed (sTHC 40.1 +/- 74.8 versus placebo 38.8 +/- 76.4, P = 0.901), or in total MME noted at two weeks (sTHC 383.6 +/- 309.8 versus placebo 367.6 +/- 246.3, P = 0.717). Self-reported pain (P = 0.581; 0.710), hours of sleep per night (P = 0.103; 0.140), and nausea/vomiting (P = 0.689; 0.158) showed no differences between the groups at two and four weeks. No differences in patient-reported outcome measures at six weeks were noted between groups. There were no drug- or placebo-related complications noted in either group. Conclusions: Despite enthusiasm for cannabis after orthopaedic surgical procedures, this sTHC does not appear to limit opioid intake after primary TKA. Based on these data, THC may offer no benefit for patients after TKA.
Citation
Jennings JM, Dennis DA, Miner TM, Yang CC, Hemmerle MR, Johnson RM A Synthetic Form of Cannabinoid Does Not Decrease Opioid Use After Total Knee Arthroplasty: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Study. The Journal of Arthroplasty (2026). PubMed 41967982 · DOI
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Condition: Postoperative pain Topic: Opioid Topic: THC
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Reviewed by Dr. Caplan on September 17, 2026.
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